AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training

Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia, USA.
Nature Neuroscience (Impact Factor: 16.1). 03/2011; 14(3):351-5. DOI: 10.1038/nn.2739
Source: PubMed


Two intermingled hypothalamic neuron populations specified by expression of agouti-related peptide (AGRP) or pro-opiomelanocortin (POMC) positively and negatively influence feeding behavior, respectively, possibly by reciprocally regulating downstream melanocortin receptors. However, the sufficiency of these neurons to control behavior and the relationship of their activity to the magnitude and dynamics of feeding are unknown. To measure this, we used channelrhodopsin-2 for cell type-specific photostimulation. Activation of only 800 AGRP neurons in mice evoked voracious feeding within minutes. The behavioral response increased with photoexcitable neuron number, photostimulation frequency and stimulus duration. Conversely, POMC neuron stimulation reduced food intake and body weight, which required melanocortin receptor signaling. However, AGRP neuron-mediated feeding was not dependent on suppressing this melanocortin pathway, indicating that AGRP neurons directly engage feeding circuits. Furthermore, feeding was evoked selectively over drinking without training or prior photostimulus exposure, which suggests that AGRP neurons serve a dedicated role coordinating this complex behavior.

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    • "Here, we show that, in contrast, P2Y6 directly activates AgRP neurons in the ARH to potently promote feeding, while it only has minor effects on the activation of anorexigenic POMC neurons. This notion is consistent with the robust activation of feeding upon optogenetic or pharmacogenetic activation of AgRP neurons (Aponte et al., 2011; Krashes et al., 2011) and their previously defined crucial role for the maintenance of feeding, as evidenced by toxin-mediated ablation of these cells in adult mice (Gropp et al., 2005; Luquet et al., 2005). Besides our demonstration that AgRP neurons express P2Y6 and that AgRP neuron activity is required to promote feeding in response to centrally applied UDP, we reveal that UDP triggers pERK phosphorylation and increased action potential firing in a substantial proportion of AgRP neurons. "
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